Electrical stimulation of the sympathetic nerve chain

ABSTRACT

The present invention provides a method of affecting physiological disorders by stimulating a specific location along the sympathetic nerve chain. Preferably, the present invention provides a method of affecting a variety of physiological disorders or pathological conditions by placing an electrode adjacent to or in communication with at least one ganglion along the sympathetic nerve chain and stimulating the at least one ganglion until the physiological disorder or pathological condition has been affected.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.10/001,923, filed on Oct. 23, 2001, which is a continuation-in-part ofU.S. application Ser. No. 09/488,999 filed on Jan. 20, 2000; U.S.application Ser. No. 09/490,617 filed on Jan. 25, 2000; U.S. applicationSer. No. 09/511,839 filed on Feb. 24, 2000; and U.S. application Ser.No. 09/511,841 filed on Feb. 24, 2000.

BACKGROUND OF THE INVENTION

Currently, electrical stimulation of the brain with implanted electrodesis approved for use in the treatment of various movement disordersincluding Parkinson's and essential tremor. Electrical stimulation isalso approved for use in the treatment of tremors in refractoryParkinson's. The principle behind these approaches involves disruptionand modulation of hyperactive neuronal circuit transmission at specificsites in the brain. This is achieved by implanting tiny electrodes atthese sites to sense aberrant electrical signals and to send electricalpulses to locally disrupt the neuronal transmission.

It has been recognized that electrical stimulation holds significantadvantages over alternative methods of treatment. Lesioning tissuedestroys all nerve activity and generally causes collateral damage.While there are a variety of different techniques and mechanisms thathave been designed to focus lesioning directly onto the target nervetissue, collateral damage is inevitable. Even when it is possible todirect all lesioning energy onto the target nerve cluster, it is asignificant drawback that other functioning of the nerves is lost. Inaddition, there are several common side effects to lesioning describedin the medical literature. It is because of the development of these andother side effects, including the poor response of medical or surgicaltherapy especially after a delay in treatment, that thoracic or lumbarsympathectomy has not enjoyed a greater popularity among physicians.

SUMMARY OF THE INVENTION

The present invention provides a method of affecting physiologicaldisorders by placing at least one stimulation electrode at a specificlocation along the sympathetic nerve chain. Preferably, the presentinvention provides a method of affecting a variety of physiologicaldisorders or pathological conditions by placing an electrode adjacent toor in communication with at least one ganglion along the sympatheticnerve chain.

The method comprises the steps of placing an electrode adjacent to or incommunication with at least one ganglion along the sympathetic nervechain; applying an electric signal to the electrode to stimulate the atleast one ganglion; and adjusting at least one parameter of the electricsignal until the physiological disorder has been demonstrably affected,modulated, treated, alleviated, arrested, or ameliorated. The at leastone ganglion along the sympathetic nerve chain may be any cervicalganglion or ganglia, thoracic ganglion or ganglia, lumbar ganglion organglia, or sacral ganglia or any combination thereof associated with aparticular physiological disorder to be affected, modulated, treated,alleviated or ameliorated.

The stimulation may be used alone or in combination with chemical orpharmaceutical administration of active agents at the stimulation siteor remotely to affect the organ or tissue that is impacted byelectrostimulation of the sympathetic nerve chain.

The method of therapeutically treating a physiological disorder over apredetermined time period by means of an implantable pump and a cathetercomprising the steps of: implanting at least one electrode having astimulation portion that lies adjacent a predetermined stimulation sitealong the sympathetic nerve chain; implanting the catheter that has adischarge portion that lies adjacent a predetermined infusion site alongthe sympathetic nerve chain; coupling the electrode to a signalgenerator; operating said signal generator to treat said physiologicaldisorder by stimulating said stimulation site during at least a portionof the predetermined time period; and operating the pump to treat thephysiological disorder by discharging a predetermined dosage of at leastone drug through the discharge portion of the catheter into the infusionsite during at least a portion of the predetermined time period, wherebythe physiological disorder is treated.

The aforementioned method may further comprise the steps of: generatinga sensor signal related to activity resulting from said physiologicaldisorder; and regulating said steps operating the signal generator andoperating the pump in response to the sensor signal. Preferably, asensor that is implanted into the body generates the signal. Preferably,the regulation step is accomplished by a microprocessor.

A number of treatment regiments utilizing electrical stimulation can beemployed for a vast array of physiological disorders or pathologicalconditions associated with the sympathetic and parasympathetic nervoussystem. Physiological disorders that may be treated include, but are notlimited to, hyperhydrosis, complex regional pain syndrome and other painsyndromes such as headaches, cluster headaches, abnormal cardiacsympathetic output, cardiac contractility, excessive blushing condition,hypertension, renal disease, heart failure, angina, hypertension, andintestinal motility disorders, dry eye or mouth disorders, sexualdysfunction, asthma, liver disorders, pancreas disorders, and heartdisorders, pulmonary disorders, gastrointestinal disorders, and biliarydisorders. The number of disorders to be treated is limited only by thenumber, variety, and placement of electrodes (or combinations ofmultiple electrodes) along the sympathetic nervous system. Furthermore,complications can be minimized to a large extent, or possiblyeliminated, by the use of chronic or intermittent electrical stimulationand/or sensing aberrant neuronal signaling continuous or intermittentdrug infusion. The reasons are many, and include the possibility ofchanging which contacts of a multipolar lead are stimulated to minimizestimulating a portion of the ganglion. Adjusting parameters such asfrequency or pulse width of the electronic stimulation should alsominimize adverse consequences and increase beneficiary effects.

One aspect of the present invention is the stimulation of a sympatheticganglion or ganglia to treat a disease irrespective of aberrant neuronalsignaling. In other words, the methods and devices of the presentinvention may be used to treat diseases via the sympathetic ganglia, notjust disorders associated with or as a result to diseased sympatheticsignals.

According to one embodiment of the present invention, a method ofaffecting heart contractility in a patient comprises placing anelectrode in communication with at least one ganglion along thesympathetic nerve chain of the patient wherein the at least one ganglionis associated with heart contractility; applying an electric signal tothe electrode to stimulate the at least one ganglion; and adjusting atleast one parameter of the electric signal until heart contractility hasbeen affected. Preferably, the at least one ganglion is selected fromthe group consisting of T-1 through T-4 ganglia, cervical ganglia, andcombinations thereof.

Preferably, the application of the electrical signal to stimulate the atleast one ganglion is effective in modulating heart contractility. Inthis embodiment, the patient may have heart failure associated withcardiomyopathy or may have a heart contractility disorder where theheart contractility disorder may be cardiomyopathy or hypertrophiccardiomyopathy.

The method may further comprise administering an amount of apharmaceutical agent to the at least one ganglion wherein the amount isdetermined based upon the effectiveness of the electrical stimulation ofthe at least one ganglion. The administration may be accomplished by acatheter coupled to a pump wherein the catheter is placed incommunication with the at least one ganglion along the sympathetic nervechain of the patient. The method may further comprise sensing a signalrelated to heart contractility wherein the signal may be an electricalsignal or a chemical signal. Preferably, the method further comprisesregulating the electrical stimulation in response to the signal.

According to another embodiment of the present invention, a method ofaffecting coagolapathies in a patient comprises placing an electrode incommunication with at least one ganglion along the sympathetic nervechain of the patient wherein the at least one ganglion is associatedwith a coagolapathy; applying an electric signal to the electrode tostimulate the at least one ganglion; and adjusting at least oneparameter of the electric signal until the coagolapathy has beenaffected. Preferably, the at least one ganglion is selected from thegroup consisting of T-1 through T-4 ganglia, cervical ganglia, andcombinations thereof.

Preferably, the electrical stimulation is effective in releasing tissueplasminogen activator or angiotensin II.

The method may further comprise administering an amount of apharmaceutical agent to the at least one ganglion wherein the amount isdetermined based upon the effectiveness of the electrical stimulation ofthe at least one ganglion. The administration may be accomplished by acatheter coupled to a pump wherein the catheter is placed incommunication with the at least one ganglion along the sympathetic nervechain of the patient. The method may further comprise sensing a signalrelated to the coagolapathy wherein the signal may be an electricalsignal or a chemical signal. Preferably, the method further comprisesregulating the electrical stimulation in response to the signal.

According to another embodiment of the present invention, a method ofaffecting a bronchial disorder in a patient comprising placing anelectrode in communication with at least one ganglion along thesympathetic nerve chain of the patient wherein the at least one ganglionbeing associated with the bronchial disorder; applying an electricsignal to the electrode to stimulate the at least one ganglion; andadjusting at least one parameter of the electric signal until thebronchial disorder has been affected. Preferably, the at least oneganglion is selected from the group consisting of T-1 through T-4ganglia, cervical ganglia, and combinations thereof.

The method may further comprise administering an amount of apharmaceutical agent to the at least one ganglion wherein the amount isdetermined based upon the effectiveness of the electrical stimulation ofthe at least one ganglion. The administration may be accomplished by acatheter coupled to a pump wherein the catheter is placed incommunication with the at least one ganglion along the sympathetic nervechain of the patient.

The method may further comprise sensing a signal related to thebronchial disorder wherein the signal may be an electrical signal or achemical signal. Preferably, the method further comprises regulating theelectrical stimulation in response to the signal.

The following parameters related to the electrical signal apply to theaforementioned embodiments and embodiments discussed in greater detailherein. The electrical signal to stimulate the at least onepredetermined site may be continuous or intermittent. The electrode maybe either monopolar, bipolar, or multipolar. Preferably, the oscillatingelectrical signal is operated at a voltage between about 0.1 .mu.V toabout 20 V. More preferably, the oscillating electrical signal isoperated at a voltage between about 1 V to about 15 V. Formicrostimulation, it is preferable to stimulate within the range of 0.1.mu.V to about 1 V. Preferably, the electric signal source is operatedat a frequency range between about 2 Hz to about 2500 Hz. Morepreferably, the electric signal source is operated at a frequency rangebetween about 2 Hz to about 200 Hz. Preferably, the pulse width of theoscillating electrical signal is between about 10 microseconds to about1,000 microseconds. More preferably, the pulse width of the oscillatingelectrical signal is between about 50 microseconds to about 500microseconds. Preferably, the application of the oscillating electricalsignal is: monopolar when the electrode is monopolar; bipolar when theelectrode is bipolar; and multipolar when the electrode is multipolar.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic of the Autonomic Nervous System illustratingsympathetic fibers and parasympathetic fibers;

FIG. 2 is a schematic illustration of a patient lying in the lateraldecubitus position having one visualization port in the fifthintercostal space at the mid-axillary line and two instrument ports atthe fourth and fifth intercostal space at the anterior and posterioraxillary lines, respectively;

FIG. 3 is an axial cross section view of the upper thoracic regionincluding one visualization port and two instrument ports wherein thetwo instrument ports have disposed therethrough endoscopic instrumentsaccessing the ipsilateral paravertebral region where the sympatheticnerve chain lies;

FIG. 4 is an exposed view of the left hemithorax displaying oneinstrument tenting the parietal pleura while the second endoscopicinstrument is incising the parietal pleura to expose the sympatheticnerve chain; and

FIG. 5 is a side view of an exposed superior thoracic ganglia in whichan electrical stimulation electrode is disposed adjacent thereto.

DETAILED DESCRIPTION OF THE INVENTION

Physiological disorders that may be treated with electrical stimulationare numerous. The cause of many of these physiological disorders may bea dysfunction in anyone or a combination of nerve clusters known asganglia, a sequence of nerve clusters extending along the outside of thespinal column which form the sympathetic nervous system. Importantly,the present invention also has applicability in treating disorders thatare not related to a dysfunction in the ganglia, but rather disordersthat may benefit from stimulation of the sympathetic ganglia. Forinstance, cardiomyopathy as a result of alcoholism may benefit fromstimulation of the sympathetic upper ganglia in the thoracic cervicalregion, but is not a result of aberrant sympathetic nerve clusters.

The sympathetic, along with the parasympathetic, nervous system can alsobe called the autonomic, or vegetative, nervous system. The autonomicnervous system is comprised of the sympathetic and parasympatheticbranches. These two branches in general have opposite functions.Furthermore, the sympathetic and parasympathetic system has a centraland a peripheral component. The central component arises from the brainand includes structures such as the frontal cortex, thalamus,hypothalamus, hippocampus, cerebellum and brainstem nuclei including thecranial nerves to name a few. These central components are connected bya vast array of ascending and descending communication tracts, whichcarry information fasciculi similar to highways of information. Theperipheral component of the autonomic nervous system extends from thecranial base to the coccyx, essentially encompassing the entire spinalcolumn. The parasympathetic group lies predominately in the cranial andcervical region, while the sympathetic group lies predominantly in thelower cervical, and thoracolumbar and sacral regions. The sympatheticperipheral nervous system is comprised of the sympathetic ganglia thatare ovoid/bulb like structures (bulbs) and the paravertebral sympatheticchain (cord that connects the bulbs). There is also an importantdistinction between the anatomical structure of the sympathetic chainand the parasympathetic chain. The sympathetic chain is a more tightbundle of nerves that send out long projections. Thus thepost-ganglionic fibers are long and go the end organ. Whereas, theparasympathetic nerves are more diffuse network/arrays of ganglia thatare very close to the end point and hence the post-ganglionic fibersfrom them are usually at the end organ. This is an important distinctionfor neuromodulation therapies since there are multiple discrete gangliaof the sympathetic system that can be affected with wide andfar-reaching effects.

The autonomic nervous system has both afferent and efferent componentsand hence stimulation/modulation can affect both the end organs(efferent) as well as the afferents—to the brain and the central nervoussystem. This is a similar concept of how the vagus nerve stimulationworks, i.e. in a reverse, afferent, or retrograde fashion.

Although sympathetic and parasympathetic fibers (axons) transmitimpulses producing different effects, their neurons are morphologicallysimilar. They are smallish, ovoid, multipolar cells with myelinatedaxons and a variable number of dendrites. All the fibers form synapsesin peripheral ganglia, and the unmyelinated axons of the ganglionicneurons convey impulses to the viscera, vessels and other structuresinnervated. Because of this arrangement, the axons of the autonomicnerve cells in the nuclei of the cranial nerves, in the thoracolumbarlateral cornual cells, and in the gray matter of the sacral spinalsegments are termed preganglionic sympathetic nerve fibers, while thoseof the ganglion cells are termed postganglionic sympathetic nervefibers. These postganglionic sympathetic nerve fibers converge, in smallnodes of nerve cells, called ganglia that lie alongside the vertebralbodies in the neck, chest, and abdomen. In particular, the stellateganglion is located laterally adjacent to the intervertebral spacebetween the seventh cervical and first thoracic vertebrae. The first,second, third and fourth thoracic ganglia lie next to their respectivevertebral bodies on either side of the thoracic cavity. The effects ofthe ganglia as part of the autonomic system are extensive. Their effectsrange from the control of insulin production, blood pressure, vasculartone heart rate, sweat, body heat, blood glucose levels, sexual arousal,and digestion.

The present invention provides a method of treating physiologicaldisorders by implanting at least one stimulation electrode at a specificlocation along the sympathetic nerve chain. Preferably, the presentinvention provides a method of therapeutically treating a variety ofphysiological disorders or pathological conditions by surgicallyimplanting an electrode adjacent or in communication to a predeterminedsite along the sympathetic nerve chain on the affected side of the bodyor, if clinically indicated, bilaterally. FIG. 1 illustrates a schematicof the autonomic nervous system illustrating sympathetic fibers andparasympathetic fibers.

In many instances, the preferred effect is to stimulate or reversiblyblock nervous tissue. Use of the term “block” or “blockade” in thisapplication means disruption, modulation, and inhibition of nerveimpulse transmission. Abnormal regulation can result in an excitation ofthe pathways or a loss of inhibition of the pathways, with the netresult being an increased perception or response. Therapeutic measurescan be directed towards either blocking the transmission of signals orstimulating inhibitory feedback. Electrical stimulation permits suchstimulation of the target neural structures and, equally importantly,prevents the total destruction of the nervous system. Additionally,electrical stimulation parameters can be adjusted so that benefits aremaximized and side effects are minimized.

A variety of approaches are available for upper thoracic implantation ofelectrodes. Three commonly employed procedures can be adapted forelectrode implantation; they are: posterior paravertebral thoracicsympathectomy, thoracoscopic sympathectomy, and retroperitoneal lumbarsympathectomy. Reference is made to “Surgical Management of Pain”,Thieme Medical Publishers, Inc. RD 595.5.587 (2001) incorporated in itsentirety herein by reference thereto for further details. For opensurgery, anterior supraclavicular, transaxillary, and posteriorparavertebral approaches are used. Modification of a posteriorparavertebral approach is favored by most neurosurgeons. Unlike otherapproaches, the route does not require separate incisions for bilateralproblems. It provides a more direct exposure of the sympathetic gangliaand their rami communicantes. The open surgical options are generallylimited for lumbar electrode placement as the retroperitoneal flankapproach is predominantly used. Even with improved surgical techniques,open techniques are relatively invasive procedures. The development ofvideo-assisted endoscopic imaging and improved instrumentation duringthe past decade has let to an increase in endoscopic procedures. Theupsurge in the enthusiasm for endoscopic procedures should carry overfor lumbar electrode implantation. Percutaneous radiofrequency thoracicimplantation technique would appear to offer significant advantages asto the placement of electrodes. It is even less invasive than theendoscopic procedures and an improvement over other percutaneoustechniques. This procedure can be done on an outpatient basis withintravenous sedation and local anesthesia; however, it has not gainedwidespread acceptance because of the high degree of technical difficultywith localization. Real-time intraoperative magnetic resonance imaging(MRI) may be useful in localizing the lumbar sympathetic ganglia.

The present invention avoids a number of the disadvantages previouslyseen with sympathectomies and the like. The ability to neuromodulate andto detect when and to what degree neuromodulation is necessary isextremely important. The electrode itself may be designed to shield theportion of the electrode not exposed to the ganglia. Also, the electrodemay be fixed to the bone, soft tissue, ribs, or vertebra body. All thatis required is that the electrode be exposed or in contact with thedesired ganglia of the sympathetic nerve chain.

Preferably collateral stimulation of the muscle is avoided while soavoiding compression of the ganglia to avoid nerve death. Theinnervation of the sympathetic nerve chain provides ample opportunity toutilize the methods and devices of the present invention. The electrodeitself may be implanted within the ganglia.

Referring now to FIG. 2, a patient 100 is illustrated in the decubitusposition where the hips of the patient 100 are preferably below theflexion joint of the operating room table. Subsequent flexion of thetable allows some separation of the ribs by dropping the patient's hipsand therefore increasing the intercostal space to work through. Theipsilateral arm is abducted on an arm holder. Rotating the tablesomewhat anteriorly and using reverse Trendelenburg positioning furthermaximizes the exposure to the superior paravertebral area by allowingthe soon to be deflated lung (see FIGS. 3 and 4) to fall away from theapical posterior chest wall. This is the preferred position of thepatient 100 prior to performing the procedure as this position exposesthe vertebral bodies where the sympathetic nerve chain liesextrapleurally.

The procedure begins with placing the patient 100 under generalanesthesia and intubated via a double lumen endotracheal tube. Thedouble lumen endotracheal tube permits ventilation of one lung andcollapsement of the other lung that is to be operated upon without usingcarbon dioxide insufflation. One incision is made in the midaxillaryline in the fifth intercostal space that is identified as port 104. Port104 can be used for various reasons, but it is preferred that port 104is used as a telescopic video port which will provide video assistanceduring the procedure. While under endoscopic observation, a secondincision is made in the third or fourth intercostal space at theanterior axillary line that is identified as port 106. Port 106 ispreferably used as an instrument channel. A third incision is made atthe posterior axillary line just below the scapular tip in the fifthinterspace that is identified as port 102. Port 106 is preferably usedas a second instrument channel. Preferably, the three incisions madeduring the thoracoscopic sympathectomy are approximately 2 cm in length.Additional incisions (i.e., ports) can be made as necessary.

Referring now also to FIGS. 3 and 4, in which axial cross section andexposed views of the surgical signal are provided, respectively, thesurgical exposure and preparation of the relevant portion of thesympathetic nerve chain for the treatment of various physiological andpathological conditions is described. After the lung 110 is collapsed,and if necessary, retracted down by a fanning instrument via one of theworking ports, the sympathetic nerve chain 112 is visualized under theparietal pleura 114 as a raised longitudinal structure located at thejunction of the ribs 116 and the vertebral bodies 118. The parietalpleura 114 is grasped between the first and second ribs in the regionoverlying the sympathetic nerve chain 112 and scissors 120 or anendoscopic cautery is used to incise the parietal pleura 114 in avertical manner just below the first rib thereby exposing thesympathetic nerve chain 112.

Referring now also to FIG. 5, in which the implantation of amultichannel stimulation electrode 122 at a specific location of thesympathetic nerve chain is shown, the implantation of the stimulationelectrode 122 is now described. Once the sympathetic nerve chain 112 hasbeen exposed, a multichannel stimulation electrode 122 is implantedadjacent to a predetermined site along the sympathetic nerve chain thatis associated with the physiological disorder or pathological conditionbeing treated. Preferably, predetermined site along the sympatheticnerve chain, which is associated to the physiological disorder orpathological condition being treated, is directly into or adjacent toany single ganglion along the sympathetic nerve chain or any combinationof ganglia along the sympathetic nerve chain. The stimulation electrode122 is preferably sutured in place to the nearby tissue or parietalpleura 114. The vicinity of the sympathetic nerve chain for which thestimulation electrode is positioned depends on the physiologicaldisorder or pathological condition being treated.

The electrode 122 is connected to a power source (most likely abattery/pulse generator) which provides the energy/power source for thestimulation. The power source could be a battery implanted on oradjacent to the electrode 122 or it could be implanted at a remote siteon the head or thorax away from the site of stimulation (as in cardiacpacemakers or deep brain stimulators). The connection cable can bepassed out of the thoracic cavity via one of the neighboring surgicalports, and tunneled subcutaneously to the electrical signal sourcewhich, in turn, is operated to stimulate the predetermined treatmentsite over the sympathetic ganglia, such that the clinical effects of thephysiological disorder are reduced with minimal side effects.

Once the electrode 122 is secured in place, the electrical signal sourceis activated thereby applying an oscillating electrical signal, having aspecified pulse width, to the electrode 122. The electrode 122 may beimplanted, sutured, stapled, or otherwise secured in place. Theelectrode 122 is preferably in contact with the ganglia, but may besimply in electrical communication. The oscillating electrical signalmay be applied continuously or intermittently. Furthermore, if anelectrode is implanted directly into or adjacent to more than oneganglion, the oscillating electrical signal may be applied to oneelectrode and not the other and vice versa. One can adjust thestimulating poles, the pulse width, the amplitude, as well as thefrequency of stimulation to achieve a desired goal. The application ofthe oscillating electrical signal stimulates the area of the sympatheticnerve chain where the electrode 122 was placed. This stimulation mayeither increase or decrease nerve activity. The frequency of thisoscillating electrical signal is then adjusted until the physiologicaldisorder being treated has been demonstrably alleviated. This is thenconsidered the ideal frequency. Once the ideal frequency has beendetermined, the oscillating electrical signal is maintained at thisideal frequency. Preferably, the oscillating electrical signal isoperated at a voltage between about 0.1 .mu.V to about 20 V. Morepreferably, the oscillating electrical signal is operated at a voltagebetween about 1 V to about 15 V. For microstimulation, it is preferableto stimulate within the range of 0.1 .mu.V to about 1 V. Preferably, theelectric signal source is operated at a frequency range between about 2Hz to about 2500 Hz. More preferably, the electric signal source isoperated at a frequency range between about 2 Hz to about 200 Hz.Preferably, the pulse width of the oscillating electrical signal isbetween about 10 microseconds to about 1,000 microseconds. Morepreferably, the pulse width of the oscillating electrical signal isbetween about 50 microseconds to about 500 microseconds. Preferably, theapplication of the oscillating electrical signal is: monopolar when theelectrode is monopolar, bipolar when the electrode is bipolar, andmultipolar when the electrode is multipolar.

The electrodes or their casing may be made of inert material (silicon,metal or plastic) to reduce the risk (chance) of triggering an immuneresponse. Electrodes should be studied for suitability to MRI and otherscanning techniques. The electrodes should be anchored securely at thesite of implantation. The stimulating signal may have variableparameters including voltage, frequency, current, intensity, and polecombinations. These parameters can be modulated by setting and adjustingthe stimulus. The electrode signal (output) can be adjusted to specifiedsettings based on the degree of relief at the time of surgicalimplantation or later on following onset of acute episodes. Thedirection of current flow may need to be and is preferably reversible.The stimulating signal itself may be intermittent or continuousdepending on the setting.

The setting of the electrodes can be adjusted externally using currentlyavailable technology utilizing magnetic signals conventional telemetry.As the technology progresses, other modalities may be used to adjust andmodulate the parameters of the stimulating electrodes. The electrodewould then be connected to the remotely placed battery via wires.

The choice of electrodes for stimulation influences how much current isrequired to produce depolarization. When the stimulating electrode isthe cathode (negative), it causes the current to flow from the cathodeto the anode (positive) along the nerve towards the electrode and causesdepolarization of the neural tissue (neurons, axons) at a much lowercurrent than when the stimulating electrode is the anode (positive).

The electrical discharge cycle (action potential) of a typical neuronmay last up to 1 millisecond and the internal voltage of the neuron maychange from −70 to +20 millivolts. Peripheral nerve stimulation can bedone by the transcutanous method where the stimulating electrodes areplaced on the skin overlying the nerve. Another mode of peripheral nervestimulation involves placing a stimulating needle electrode through thedermis adjacent and occasionally directly on the nerve. The stimulatingparameters are a function of the distance of the stimulating electrodefrom the nerve.

Electrical stimulation of the sympathetic ganglia can have a heretoforeunexpected beneficial impact on the body, particularly regarding organsor systems associated with the ganglia being stimulated. Stimulation ofthe ganglia may result in functional activation or inhibitation of thesystem associated with the particular sympathetic ganglia and nerve.These functions include affecting (increasing or decreasing) themovement of organs, the secretion of hormones or enzymes, or affectingcertain functions associated with the organ and controlled to somedegree by the sympathetic ganglia.

The following Examples break the ganglia down into region, organ orsystem, and diseases that may benefit from electrical stimulation. Thethree basic areas of ganglia location for purposes of the presentinvention are cervical ganglia, thoracic ganglia, and lumbar ganglia.The sacral region may also be a region of electrode implantation, but,technically, there are no sympathetic ganglia in the sacral region.However, nerves from other regions (e.g., lumbar) that are incommunication external to this region and may be stimulus as a means tostimulate the lumbar ganglia. Obviously, these can be further subdividedinto upper, mid, and lower regions respectively. Placement of electrodesin these regions or portions of these regions appear to have a desirableimpact on many diseases associated with the human anatomy. Although notan indication of priority of disease, the following examples areprovided to illustrate the utility and novelty of the present inventionto illustrate the utility of the present invention and are not meant tobe limiting. For purposes of brevity, a specific ganglion will berepresented by a letter and number combination or series of letter andnumber combinations (e.g., the second thoracic ganglion will berepresented as “the T-2 ganglion” and the fourth lumbar ganglion will berepresented as “the L-4 ganglion”, etc.).

Example 1

Sympathetic electrical stimulation may be used, for example, to treatcardiac disorders for which the sympathetic output is abnormally high orlow. The sympathetic pre-ganglionic fibers lay mainly in the sympathetictrunk ganglia from the superior cervical to the T-4 or T-5 ganglia andthen the post-ganglionic fibers, which are longer, go to the heartdirectly via the long cervical and thoracic sympathetic cardiac nerves.In fact, stimulation of the spinal cord relieving and increasingmicrocirculation of the heart may indeed be mediated through the spinalcord fibers which are sympathetic and which are going throughhighways/tracts in the spinal cord on their way from the centralautonomic nervous system to the sympathetic ganglia. In contrast, theparasympathetic pre-ganglionic fibers to the heart reach the heart viathe cardiac branches of the vagus nerve and relay in the ganglia of thecardiac plexus on in small subendothelial ganglia which are in orsurrounding the heart. For the purposes of providing details in thediscussion to follow, three representative examples will be stressed:heart failure, arrythmia, and angina pectoris. The most prevalent causeof death in developed countries is cardiac related. These cardiacabnormalities can vary from valvular disease to vascular disease toelectrical irregularities. The current mainstay of treatment for many ofthese disorders involves a vast array of medications, surgicalapproaches, as well as endovascular methodologies. The most commonlyemployed general treatment involves the use of medications. While manydrugs have been found to alleviate cardiac-related symptoms, very fewhave actually been demonstrated to prolong life after a myocardialinfarction. The two most commonly cited drugs with life-prolongingproperties are acetyl salicylic acid (aspirin) and beta-blockers.Beta-blockers reduce the effects of the sympathetic system on the heartvia a variety of different mechanisms, including blood pressurereduction, decreased heart rate, decreased cardiac contractility, andthus, decreased cardiac oxygen demand. Perhaps the most beneficialeffect of beta blockade, in terms of increasing survival in patientswith cardiac disease, is its anti-arrhythmic effect. These effectsprolong and enhance cardiac functionality and efficiency. Their mode ofaction involves the chemical blockade of the sympathetic efferent nervefibers that terminate on the heart. These nerve fibers originate in anerve cluster known as the stellate ganglia. Beta-blockers act byblocking the beta-adrenergic system, either non-selectively, orspecifically the beta-1 receptors which are almost exclusively found inthe heart. The non-selective beta-adrenergic blockers, such aspropranolol, also block the beta-2 system, which in susceptibleindividuals can cause life-threatening bronchospasm. As medications areadministered systemically, even the specific beta-1 blockers have knownside-effects including lethargy, hallucinations, nausea, diarrhea,impotence, hypoglycemia without the normally accompanying tachycardia,fever, and arthralgia. Accordingly, it would appear that for any diseaseor condition for which beta-blockers are useful, the electrostimulationof the present invention would have application. An additive, or evensynergistic, effect may be seen with both beta-blockers andelectrostimulate. Electrostimulation may reduce side effects and/orefficiency of beta-blockers.

The sympathetic outflow to the heart originates in the stellate and thefirst four thoracic ganglia. The sympathetic nervous system sendssignals to the heart, increasing cardiac contractility, heart rate, andprolonging the QT-interval. In particular, the stellate ganglion, aswell as the first, second, third and fourth thoracic ganglia lie next totheir respective vertebral bodies on either side of the thoracic cavity.The left side, however, has been demonstrated to provide the majority ofthe sympathetic output to the heart. Minimal changes in cardiacparameters are seen when stimulating or lesioning the right side. Infact, left side stellate ganglion stimulation in humans has beendemonstrated to effect the ejection fraction of the heart, the QTinterval, and blood pressure.

Stimulation of the sympathetic ganglion (stellate and cervical) in dogshas been shown to modulate the levels of angiotensin II. Accordingly,stimulation of the sympathetic ganglion may benefit the angiotensinsystem. Angiotensin II is a compound (octapeptide) that is involved inpathophysiology of multiple cardiac, vascular and renal diseases.Angiotensin II is known to influence cardiac function and has been shownto effect coronary artery smooth muscle cells, endothelium andsympathetic nerve endings. Aberrant functioning of the Renin-angiotensinsystem has also been implicated in hypertension and renal disorders. Avariety of pharmacological therapies are aimed at blocking theproduction and/or the receptors for angiotensin II. The involvement ofthe local angiotensin system in ganglionic functions was discussed inthe article “Upregulation of Immunoreactive Angiotensin II Release andAngiotensinogen mRNA Expression by High Frequency PreganglionicStimulation at the Canine Cardiac Sympathetic Ganglia” by Kushiku et al.published in Circulation Research, Pgs. 110-116, Jan. 5/19, 2001 whichis hereby incorporated by reference in its entirety.

Also, sympathetic stimulation may also benefit hypercoagulation,prothrombotic states. Sympathetic neurons synthesize, transport andstore tissue plasminogen activator (TPA) at the axonal terminals thatinnervate the vessel wall. Sympathetic stimulation induces a surge ofTPA from the vessel wall into the blood. TPA is a protein that hasanti-thrombotic/clotting effects (i.e., it essentially dissolvesmicroclots). Sympathetic ganglionic stimulation may be helpful inpatients with systemic clotting problems.

Regarding the treatment of abnormal cardiac sympathetic output (e.g.,angina pectoris or heart failure), the stimulation electrode 122 isimplanted over the inferior third of the stellate ganglion. Preferably,the stimulation electrode 122 is implanted over the inferior third ofthe stellate ganglion and over the upper thoracic ganglia. Morepreferably, the electrode 122 is implanted over the inferior third ofthe stellate ganglion and over the T-1, T-2, T-3 and T-4 ganglia. Forexample, for a patient with angina pectoris who is post-myocardialinfarction, one wishes to decrease heart rate and oxygen consumption, aswell as increase heart rate variability, all of which have beendemonstrated to have a positive prognostic outcome. By stimulating at ahigh frequency, the sympathetic outflow would be inhibited. In a patientwith cardiac failure on the other hand, stimulating at a low frequencywould drive sympathetic flow and would increase cardiac contractilityand cardiac output. Adjusting the frequency, in particular, can eitherdrive (increase) or inhibit sympathetic output to the heart to achievedesired effects. Thus, the thoracic ganglia may support not onlyvasodilatory or vasoconstrictive effects of the vascular system, butalso the contractility of the heart. Implantation of the electrode 122over the lower thoracic ganglia may also affect hormonal release forhypertension.

Example 2

Complex regional pain syndrome (CRPS) type I, commonly known as reflexsympathetic dystrophy syndrome, or RSDS, was described 25 years ago.Several synonyms have been commonly employed in describing parts or allof this syndrome, including Raynaud's syndrome, vasomotor instability,occupational digital thrombosis, arteriosclerotic obliterative disease,etc. CPRS Type II, on the other hand, also known as causalgia, is aregional pain syndrome that develops after injury to a peripheral nerve,as first described during the Civil War by Dr. W. Mitchell. Spontaneouspain develops in the territory of the affected nerve that may thenspread beyond that region. Vasomotor abnormalities and focal edema mayoccur alone or in combination in both CRPS types I and II. These are aseverely disabling group of illness with simultaneous involvement ofnerve, skin, muscle, blood vessels, and bones. While there are manysymptoms associated with CRPS, the only common denominator is pain. Thepain usually appears in one or more extremities, and is described aschronic, burning and constant in nature. A syndrome of total body paindue to CRPS has been described as well. The remainder of symptoms may ormay not occur. These symptoms include swelling, limited motor functionwhich may lead to atrophy or dystrophy, tremor focal dystonia or spasm,skin changes such as atrophy, dryness, and scaling, as well as bonychanges with joint tenderness and swelling. In addition, vasomotorinstability consisting of Raynaud's phenomenon (e.g. color changes andpain in fingers when exposed to cold), vasoconstriction or dilatationleading to cold and warm extremities respectively, as well as increasedsweating.

The cause of the condition is currently not well understood and is oftenunrecognized. A number of precipitating factors have been associatedwith CRPS including minor trauma, cerebral or spinal cord lesions,ischemic heart disease and/or myocardial infarction, and repetitivecumulative trauma, such as carpal tunnel syndrome. However, in many ofthe patients a definite precipitating event can not be identified.Duration of CRPS varies, in many cases the pain continues on for atleast two years and in some cases, indefinitely. Some patientsexperience periods of remissions and exacerbations. Periods of remissionmay last for weeks, months or years. The mean age of onset is in themid-thirties and there is increasing evidence that the incidence of CRPSin adolescents and young adults is on the rise. In Germany alone, forexample, the annual incidence of RSD is estimated at 15,000. Both sexesare affected, but the incidence of the syndrome is higher in women.Nonsurgical treatment consists of medicinal therapy, physical therapy,various peripheral or sympathetic nerve blocks, transcutaneouselectrical nerve stimulation, or surgical sympathectomy. Patientresponse to therapy directly correlates to early diagnosis andtreatment. However, the overall response rate to treatment is poor withover 50% of patients having significant pain and/or disability yearslater.

Regarding the treatment of complex regional pain syndrome Type I(specifically upper extremity reflex sympathetic dystrophy), thestimulation electrode 122 is implanted over the inferior portion of thestellate ganglion. Preferably, the stimulation electrode 122 isimplanted over the inferior portion of the stellate ganglion and overthe upper thoracic ganglia. More preferably, the stimulation electrode122 is implanted over the inferior third of the stellate ganglion andover the T-2, T-3, and T-4 ganglia.

Example 3

Hyperhydrosis is characterized by excessive sweating. The disorder canbe quite pronounced, and it affects hundreds of thousands of patients,many of who are not simply embarrassed by the condition, but are in facttruly handicapped. These handicaps include constant wiping of hands,social avoidance, work avoidance, and difficulty performing tasks suchas holding a steering wheel while driving. It has been estimated that0.1-0.2% of young adults suffer from severe palmar hyperhydrosis.

In patients suffering from palmar or other forms of hyperhydrosis, thefirst, second, third and fourth thoracic ganglia play a major role inthe abnormal signal generation to the sweat glands of the hand.Presently, there is no effective medicinal treatment for the condition.The present standard of care for the interventional treatment of palmarhyperhydrosis is the lesioning of the stellate and upper thoracicganglia via one of several surgical approaches.

Regarding the treatment of palmar or axillary hyperhydrosis, theelectrode 122 is implanted over the inferior portion of the stellateganglion. Preferably, the stimulation electrode 122 is implanted overthe inferior third of the stellate ganglion and over the upper thoracicganglia. More preferably, the stimulation electrode 122 is implantedover the inferior portion of the stellate ganglion and over the T-2,T-3, and T-4 ganglia.

Example 4

Facial blushing is excessive and frequent redness of the face that iseasily elicited by emotional or social stimuli. The instantaneousappearance of blushing is produced by normal events in daily life suchas eating with other people, meeting someone, shopping, speaking inpublic, and so on. The disorder can be quite pronounced, and it effectsa significant percentage of people who suffer from social phobia. Theprevalence rate of social phobia is approximately 10%, or 30 millionpeople in the United States alone. While many in the medical communityconsider facial blushing trivial or normal, many patients, in fact,state that it causes a significant negative impact on their quality oflife. In a recent study of 244 patients undergoing ablative surgery forthis disorder, 17% of patients were forced to take periodic sick leaveor early retirement. Suicide was considered among a quarter of patients,while half of patients used alcohol as a means of relieving their facialblushing.

Normal blushing of skin, and in particular, the face, is a reflection ofthe vasodilatory effects of blood vessels in the skin caused byemotional stimuli. This effect is mediated by the sympathetic nervoussystem originating in the upper thoracic portion of the sympatheticchain. In patients suffering from facial blushing, the first, second,and third thoracic ganglia play a major role in the abnormal signalgeneration to the blood vessels of the face and neck. Presently, thereis no effective medicinal treatment for the condition. In theaforementioned study, 22% of patients had tried medications calledbeta-blockers with minimal or no relief. Many patients also undergoexpensive psychological treatments, such as cognitive and behavioraltherapies, without significant relief of symptoms. The present standardof care for the interventional treatment of facial blushing is thelesioning of the stellate and upper thoracic ganglia via one of severalsurgical approaches.

Regarding the treatment of facial blushing, the stimulation electrode122 is implanted over the inferior portion of the stellate ganglion.Preferably, the stimulation electrode 122 is implanted over the inferiorthird of the stellate ganglion and over the upper thoracic ganglia. Morepreferably, the stimulation electrode 122 is implanted over the inferiorportion of the stellate ganglion and over the T-1, T-2, and T-3 ganglia.

Example 5

Stimulation of the T-6 through T-12 ganglia as well as the lumbarsympathetic ganglia innervates the intestines and may be helpful intreating gastrointestinal motility disorders. Also, electricalstimulation of the thoracic sympathetic ganglia may be helpful intreating GI, bowel, and visceral pain as well as that of hepatic andbiliary pain. Furthermore, stimulation of the lumbar sympathetic gangliaand sacral sympathetic nerves may be helpful in treating pelvic pain(colon, interstitial cystitis, bladder, ovaries and other reproductiveorgans) and pain of the lower extremities including RSD/CRPS.Additionally, electrical stimulation of the lower thoracic and lumbarsympathetic ganglia and sacral sympathetic nerves may be helpful intreating bladder dysfunction and other bladder conditions.

Regarding the above disorders and conditions, the stimulation electrode122 is implanted in the lower thoracic and lumbar ganglia. Implantationof the electrode and subsequent stimulation of electrode 122 of thelower thoracic and lumbar ganglia can affect the gastrointestinal systemto increase or decrease motility of the system with application topermit intestinal gastric gallbladder, liver, and pancreatic rest instates of inflammation including cholecystitis, pancreatitis,inflammatory bowel disease and constipation. Accordingly, implantationof the electrode on the T-9, T-10, and T-11 ganglia as well aspotentially with L-1, L-2, and L-3 ganglia could affect motility of thegastrointestinal system.

Example 6

Stimulation of the lower cervical and upper thoracic sympathetic gangliamay impact the tracheal, bronchial, and pulmonary systems. Therefore,electrical stimulation of the lower cervical and upper thoracicsympathetic ganglia may be helpful in treating bronchospasm episodes orchronic spasms of the airways (asthma and other entities) by controllingthe contraction of the smooth muscles of the airways.

Accordingly, in this example, implantation of the electrode 122 over theinferior portion of the T-1 through T-5 ganglia could be a very usefulapplication of the present invention to treat asthma. Also, implantationof the electrode 122 over the inferior cervical ganglion could also beuseful to treat asthma.

Example 7

Implantation of the electrode 122 over the lower thoracic and lumbarregions may also impact renal disease or other kidney diseases.

Regarding the treatment of real disease, the electrode 122 is implantedover any one or combination of lower thoracic ganglia. Preferably, thestimulation electrode 122 is implanted over the T-5 ganglion throughT-12 ganglion.

Example 8

Stimulation of the lower thoracic and lumbar ganglia may be helpful intreating sexual dysfunction including impotence and other conditions.Implantation of electrode 122 over the lower lumbar region may impactsexual dysfunction due to the association of the sympathetic nerve withthe testicles and penis.

Regarding the treatment of sexual dysfunction or other conditions, theelectrode 122 is implanted over any one or combination of lumbarganglia. Preferably, the stimulation electrode 122 is implanted over theL-1 through L-3 ganglia.

Example 9

The T-6 through T-12 ganglia may be stimulated for innervation of thepancreas and potential modification of the pancreatic enzymes andhormones such as insulin and glucagon, lipase and others needed formetabolism. Implantation of the electrode 122 as positioned above thelumbar region may affect the pancreas. This would affect hormonalrelease for diabetes.

Regarding the treatment of pancreas or liver disorders, the electrode122 is implanted over any one or combination of the lower thoracicganglia. Preferably, the stimulation electrode 122 is implanted over theT-5 through T-12.

The aforementioned procedures can most easily be accomplished by usingexisting electrode configurations or modifications thereof, with thedistal end being more superior, and the proximal end and the connectioncable being more inferior. For disorders requiring stimulation of thethoracic ganglia, the electrode 122 can be inserted into the thoraciccavity and held in place via the posterior axillary line incision andsutured by using the other working port. The connecting cable can beleft at the posterior axillary line port after the lead has been securedwith some remaining “slack” of connecting cable being left in theinter-pleural space. The proximal end of the connecting cable/tube canbe brought out of the thoracic cavity, and via an extension cable/tube,be tunneled subcutaneously and connected to an electrical pulsegenerator or infusing pump. The pulse generator or pump may be placed inthe subcutaneous tissues of the flank area, abdominal wall area, orbuttock area, etc. Any excess fluid is suctioned from the thoraciccavity and the lung is reinflated. A suctioning chest tube may or maynot be used depending on the presence or absence of damage to thevisceral pleura of the lung. The incisions are closed, and a chest x-rayis obtained in the recovery room to ensure the lung has reinflated.Electrical stimulation or drug infusion therapy may be startedimmediately, or after a delay, allowing for some healing to occur first.

Alternatively, one may prefer not to incise the parietal pleura 114 ifelectrical stimulation is used, as the current generated may modulatethe functioning of the ganglia through the pleural surface. Pending thepreference and comfort level of the surgeon, various test procedures maybe employed to maximize the probability of future effective therapy.

Alternatively, another embodiment includes a catheter with either end-or side-apertures placed over the ganglia of interest and is connectedin a similar fashion to an infusion pump device. An infusion pump devicein accordance with this embodiment may be implanted below the skin of apatient. The device has a port into which a hypodermic needle can beinserted through the skin to inject a quantity of a liquid agent, suchas a medication or drug. The liquid agent is delivered from the devicethrough a catheter port into a catheter. The catheter is positioned todeliver the agent to specific infusion sites in the sympathetic orparasympathetic nerve chain. The infusion pump may take the form of thedevice described in U.S. Pat. No. 4,692,147 (Duggan) or U.S. Pat. No.6,094,598 (Elsberry et al.) which are both assigned to Medtronic, Inc.,Minneapolis, Minn., and are both hereby incorporated by referenceherein.

The distal end of the catheter terminates in a cylindrical hollow tubehaving a distal end implanted into a portion of the ganglia of interestin the sympathetic or parasympathetic nerve chain by conventionalstereotactic surgical techniques. The distal end is provided withmicroporous portions in the preferred embodiment; however, multipleholes or slits within portions could also be used. The tube includes anouter cylindrical insulating jacket and an inner cylindrical insulatingjacket that defines a cylindrical catheter lumen. A multifilar coil orstrands of wire is embedded in the tube.

The tube is surgically implanted through a hole in the back of a humanand the catheter is implanted at or near the ganglion of interest. Astylet may be placed into the center of the tube to give it stiffnesswhen introducing the tube into the neural tissue. After the stylet isremoved, the center lumen constitutes a catheter that can be used toinfuse an agent, including a drug. The catheter is joined to theimplanted infusion pump in the manner shown. The infusion pump isimplanted in a human body.

Alternatively, the device may be implanted in the abdomen. The cathetermay be divided into twin tubes that are implanted into the brainbilaterally as shown. Alternatively, the tube may be supplied with drugsfrom a separate catheter and pump. Referring again to a device made inaccordance with this embodiment, the device also may be implanted belowthe skin of a patient. The device may take the form of a signalgenerator Model 7424 manufactured by Medtronic, Inc. under the trademarkItrel II which is incorporated by reference.

The distal end of the tube terminates into stimulation electrodes andeach of the electrodes is individually connected to the device through aconductor in the wire. The wires exit the catheter to form a cable whichis joined to the implanted device. While an embodiment may include twoelectrodes on the tube, some applications may require a greater number.

A drug can be delivered continuously (within the constraints of theparticular delivery device being used) or it may be delivered duringintermittent intervals coordinated to reflect certain time intervalssuch as the half-life of the particular agent being infused or circadianrhythms. As an example, symptoms may normally subside at night when theperson is sleeping so the drug delivery rates might be reduced tocoincide with the hours between 10 p.m. and 7 a.m.

In addition, this embodiment is extended to include a combinationelectrical contact and drug delivery system, as well as a system thathas the capacity to sense or record electrical or chemical activity inthe region of interest. A sensor may be implanted into a portion of apatient's body suitable for detecting symptoms of the physiologicaldisorder of interest as described in U.S. Pat. No. 6,058,331 (King),assigned to Medtronic, Inc., which is hereby incorporated by referenceherein. The sensor is adapted to sense an attribute of the symptom to becontrolled or an important related symptom. The sensor may take the formof a device capable of detecting nerve cell or axon activity that isrelated to the pathways at the cause of the symptom, or that reflectssensations which are elicited by the symptom. Such a sensor may belocated deep in the brain. For such detecting, sensor may take the formof an electrode inserted into the internal capsule, motor cortex, basalganglia of the brain, spinal cord, ganglia, or nerves. Signals that arereceived by the sensor may by amplified before transmission to circuitrycontained within devices. Yet another form of the sensor would include adevice capable of detecting nerve compound action potentials (e.g.,either sensory afferent information from muscle or skin receptors orefferent motor potentials controlling a muscle of interest). The sensormay take the form of a transducer consisting of an electrode with an ionselective coating applied which is capable of directly transducing theamount of a particular transmitter substance or its breakdownby-products found in the interstitial space of a region of the brainsuch as the ventral lateral thalamus. The level of the interstitialtransmitter substance is an indicator of the relative activity of thebrain region. An example of this type of transducer is described in thepaper “Multichannel semiconductor-based electrodes for in vivoelectrochemical and electrophysiological studies in rat CNS” by Craig G.van Home, Spencer Bement, Barry J. Hoffer, and Greg A. Gerhardt,published in Neuroscience Letters, 120 (1990) 249-252.

In operation, the sensor generates a sensor signal related to theactivity resulting from the physiological disorder. A microprocessorthen regulates the stimulation in response to the sensor signal to treatthe physiological disorder. The microprocessor within the device can beprogrammed so that a controlled amount of agent or drug can be deliveredto the specific ganglia of interest. Alternatively, the sensor can beused with a closed loop feedback system to automatically determine thelevel of drug delivery necessary to alleviate the physiological disordersymptoms.

The output of the sensor is coupled by a cable comprising conductors tothe input of analog to digital converter. Alternatively, the output ofan external feedback sensor would communicate with the implanted pulsegenerator through a telemetry downlink. The output of the analog todigital converter is connected to terminals BAR and BAR shown in FIG.11A of U.S. Pat. No. 4,692,147. Before converter is connected to theterminals, the demodulator currently shown in FIG. 11A would bedisconnected.

Alternative approaches include posterior open extrapleural techniques,posterior percutaneous approaches, the anterior supraclavicular method,as well as the open transthoracic approach. However, while there hasbeen described and illustrated specific embodiments of new and novelmethods of treatment for physiological disorders, such as hyperhydrosis,facial blushing, complex regional pain syndromes, and abnormal cardiacsympathetic output, it will be apparent to those skilled in the art thatvariations and modifications are possible, such alterations shall beunderstood to be within the broad spirit and principle of the presentinvention which shall be limited solely by the scope of the claimsappended hereto.

1-23. (canceled)
 24. A method for treating a pancreatic or liverdisorder in a patient, said method comprising the steps of: placing anelectrode in electrical communication with at least one ganglion alongthe sympathetic nerve chain (SNC) of the patient, the at least oneganglion being associated with the pancreatic or liver disorder;applying an electric signal to the electrode to stimulate the at leastone ganglion; and adjusting at least one parameter of the electricsignal until the pancreatic or liver disorder has been treated.
 25. Themethod of claim 24, wherein the pancreatic or liver disorder isdiabetes.
 26. The method of claim 24, wherein the at least one ganglionis an upper, middle, or lower cervical ganglion.
 27. The method of claim24, wherein the at least one ganglion is a thoracic ganglion.
 28. Themethod of claim 27, wherein the thoracic ganglion is a T5-T12 ganglion.29. The method of claim 24, wherein applying an electric signal to theelectrode to stimulate the at least one ganglion modifies pancreaticenzymes and hormone release.
 30. The method of claim 29, whereinapplying an electric signal to the electrode to stimulate the at leastone ganglion causes release of at least one of insulin, glucagon, andlipase.
 31. The method of claim 24, wherein the electrode is placed onor in the at least one ganglion.
 32. The method of claim 24, furthercomprising the step of administering an amount of a pharmaceutical agentto the at least one ganglion.
 33. The method of claim 32, wherein theamount is determined based on the effectiveness of the electricalstimulation of the at least one ganglion.
 34. A method for treatingdiabetes in a patient, said method comprising the steps of: placing anelectrode in electrical communication with at least one ganglion alongthe SNC of the patient, the at least one ganglion innervating thepancreas; applying an electric signal to the electrode to stimulate theat least one ganglion; and wherein applying an electric signal to theelectrode modifies pancreatic enzymes and hormone release; adjusting atleast one parameter of the electric signal until the diabetes has beentreated.
 35. The method of claim 34, wherein the at least one ganglionis an upper, middle, or lower cervical ganglion.
 36. The method of claim34, wherein the at least one ganglion is a thoracic ganglion.
 37. Themethod of claim 36, wherein the thoracic ganglion is a T5-T12 ganglion.38. The method of claim 34, wherein applying an electric signal to theelectrode to stimulate the at least one ganglion causes release of atleast one of insulin, glucagon, and lipase.
 39. The method of claim 34,wherein the electrode is placed on or in the at least one ganglion. 40.The method of claim 34, further comprising the step of administering anamount of a pharmaceutical agent to the at least one ganglion.
 41. Themethod of claim 40, wherein the amount is determined based on theeffectiveness of the electrical stimulation of the at least oneganglion.
 42. A method for treating a pancreatic or liver disorder in apatient, said method comprising the steps of: placing an electrode inelectrical communication with at least one ganglion along the SNC of thepatient, the at least one ganglion being associated with the pancreaticor liver disorder; applying an electric signal to the at least oneganglion; sensing a signal related to the pancreatic or liver disorderand generating sensor signal; and regulating the electrical stimulationin response to the sensor signal.
 43. The method of claim 42, whereinthe signal is an electric signal.
 44. The method of claim 42, whereinthe signal is a chemical signal.